학술논문
Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron.
Document Type
Article
Author
Hao, Linhui; Hsiang, Tien-Ying; Dalmat, Ronit R.; Ireton, Renee; Morton, Jennifer F.; Stokes, Caleb; Netland, Jason; Hale, Malika; Thouvenel, Chris; Wald, Anna; Franko, Nicholas M.; Huden, Kristen; Chu, Helen Y.; Sigal, Alex; Greninger, Alex L.; Tilles, Sasha; Barrett, Lynn K.; Van Voorhis, Wesley C.; Munt, Jennifer; Scobey, Trevor
Source
Subject
*SARS-CoV-2 Omicron variant
*SARS-CoV-2
*MONOCLONAL antibodies
*HUMORAL immunity
*CD8 antigen
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Language
ISSN
1999-4915
Abstract
New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population. [ABSTRACT FROM AUTHOR]